Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI)
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|ClinicalTrials.gov Identifier: NCT03819894|
Recruitment Status : Recruiting
First Posted : January 29, 2019
Last Update Posted : February 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|Myocardial Infarction Sex Differences High Sensitivity Troponin||Diagnostic Test: Introduction of a lower female hs-cTn threshold||Not Applicable|
In subjects with suspected acute coronary syndromes (ACS), females are significantly less likely to undergo investigations, receive evidence-based treatments, and consistently have worse outcomes than males. The gap in outcomes is particularly marked among adults < 55 years of age. Sex differences in symptom presentation and in the diagnostic threshold for cardiac biomarkers have been suggested as reasons for the under-diagnosis and under-treatment of women. Cardiac troponin (cTn) T and I are proteins specific to the myocardium, which with elevated and changing concentrations detected in the blood, along with signs or symptoms consistent with myocardial ischemia, are indicative of a diagnosis of myocardial infarction (MI). With the introduction of high-sensitivity (hs) cTn tests, which allow the detection of very low concentrations of troponin, it has become evident that the level of cTn in a healthy population is approximately two-fold higher in males than in females.
Consequently, the 99th percentile threshold for cTn, the reference value used in diagnosis of MI, is lower in females compared to males. Despite this evidence and recent guidelines recommending the use of sex specific thresholds, a single, overall cTn threshold is still being used for diagnosis of MI, in both men and women, in most clinical settings.
There is mounting evidence from several jurisdictions that the rate of MI is increasing among younger females, and that there is a persistent under-diagnosis, under-treatment, and high risk of adverse outcomes among females, especially younger females, compared to their male counterparts. A better approach to the diagnostic assessment of females presenting to the emergency department (ED) with chest pain is therefore urgently needed. Additionally, several Canadian hospitals have recently made the transition from sensitive to high sensitivity cTn assays, allowing for the examination of subtle but important sex-specific differences in cTn concentrations. With this background, the investigators propose a nationwide, randomized clinical trial (RCT) to determine whether establishing female thresholds results in improved diagnosis and treatment of MI and therefore improved prognosis in women.
To determine whether the use of female hs-cTn thresholds in the assessment of women presenting to the ED with chest pain suggestive of cardiac ischemia, improves diagnostic assessment, treatment and 1-year outcomes. Specifically, the investigators will examine the impact of using female hs-cTn thresholds on:
- Diagnostic and therapeutic strategies;
- Prognosis: 1-year all-cause mortality, non-fatal MI, incident heart failure (HF) hospitalization or emergent/urgent coronary revascularization;
- Costs of diagnostic testing and treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24000 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Stepped-wedge cluster-randomized trial. Unidirectional crossover design where clusters cross over sequentially, in random order, from the control to intervention phase.|
|Masking:||Double (Participant, Outcomes Assessor)|
|Primary Purpose:||Health Services Research|
|Official Title:||Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women|
|Actual Study Start Date :||February 8, 2020|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2023|
The intervention is the introduction of a lower female threshold. In cluster-randomized trials, the cluster (i.e., hospital) is the unit of randomization.
Diagnostic Test: Introduction of a lower female hs-cTn threshold
The new female hs-cTn threshold will be baed on current recommendations for each of the assays used (hs-cTn T and I). The hospitals are the unit of randomization. At 5-month intervals, randomly selected hospitals will be advised that they are to transition to the intervention phase. For all men, the standard of care, overall population threshold will be used throughout the entire study.
No Intervention: Control
The control phase will be standard of care, with the use of an overall population hs-cTn T and I threshold, for both men and women, to identify those with myocardial injury/infarction.
- Number of patients with all-cause mortality, non-fatal myocardial infarction, hospitalization for incident heart failure, or urgent/emergent coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery) [ Time Frame: 1-year post index emergency department presentation ]
- Number of patients with a) Non-fatal myocardial infarction or all-cause mortality; b) Urgent/emergent coronary revascularization or all-cause mortality; c) Hospitalization for heart failure or all-cause mortality. [ Time Frame: 1-year post index emergency department presentation ]
- Proportion of patients who fill at least one prescription for evidence-based cardiac medications [ Time Frame: Within 90 days of ED visit ]Medications include beta-blockers, Angiotensin Converting Enzyme (ACE)-I/Angiotensin II receptor blockers (ARB), statins, anti-platelets
- Proportion of patients who undergo diagnostic tests [ Time Frame: Within 90 days of ED visit ]Diagnostic tests include nuclear medicine cardiac scan, exercise stress test, diagnostic cardiac catheterization/CT angiogram or echocardiogram
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03819894
|Contact: Mona Izadnegahdar, PhD||604-6822344 ext firstname.lastname@example.org|
|Contact: Salima Jutha, CCRA||604-806-9119||CodeMI@icvhealth.ubc.ca|
|Canada, British Columbia|
|St. Paul's Hospital||Recruiting|
|Vancouver, British Columbia, Canada|
|Contact: Mona Izadnegahdar, PhD email@example.com|
|Principal Investigator:||Karin Humphries, DSc||Medicine, Cardiology, UBC, BC Centre for Improved Cardiovascular Health|